Permanently radially compressed column

ABSTRACT

An embodiment of the present invention features a chromatographic device. The chromatographic device comprises a body having a cylindrical wall having an exterior diameter. The cylindrical wall is flexible, expanding and contracting in response to radial pressure. The cylindrical wall defines a cavity for holding a chromatographic media. A chromatographic media is retained within said cavity. A spring element surrounds the cylindrical wall, permanently radially compressing said cylindrical wall and opposing the expansion of the wall in response to internal pressure within the cavity. The radial compression prevents the movement of the chromatographic media in the cavity and the opening of channels about the walls of the body.

This application is a continuation of the U.S. patent application Ser.No. 09/525,635, filed Mar. 14, 2000, now U.S. Pat. No. 6,348,150, whichis a continuation in part of U.S. patent application No. U.S. 09/079,994filed May 15, 1998, now abandoned.

FIELD OF THE INVENTION

The present invention relates generally to high performance liquidchromatography (HPLC), and more specifically to HPLC columns.

BACKGROUND OF THE INVENTION

Chromatography is a method by which components of a solution phase areseparated by the different affinities exhibited by the components for astationary phase. Chromatography has become an important tool formeasuring the compositions of materials used in the chemical,pharmaceutical, biotechnological, and food industries.

HPLC instruments are comprised of pumps for delivering and movingsolvents (the mobile phase), an injector to introduce a sample ofinterest into the flow of the mobile phase, a tubular column encasement,containing a packed material or bed (the “stationary phase”), and adetector to register the presence and amount of different components inthe mobile phase. When the mobile phase is passed through the stationaryphase, each component will emerge from the column at a different timebecause different component in the sample will have different affinitiesto the packing material. The presence of a particular component in themobile phase exiting the column can be detected by measuring changes inphysical or chemical properties of the eluent. By plotting thedetector's signal over time, response “peaks” corresponding to thepresence of each of the components of the sample can be observed andrecorded.

The resolution between response peaks in a chromatographic analysis or“run” depends, in part, on providing a uniform and reproducible flow ofthe mobile phase through the stationary phase. Irregularities or changesin the packing material in the column from run to run adversely affectreproducibility of runs, and the reliability of the chromatographicanalysis. For example, voids in the packed bed create flowirregularities, leading to overlapping responses or muted responsepeaks.

The chromatography column encasement is typically stainless steel. Thisencasement is tightly packed with the stationary phase material byslurry packing, by tapping, or by mechanical ramming.

Within rigid-wall steel columns, voids can occur not only within thepacking, but also at the interface between the packing and theencasement wall. This leads to a phenomenon referred to as side or wallchanneling, where the mobile phase travels down the wall of the columneffectively bypassing the packing or stationary phase. Such sidechanneling decreases the reliability and reproducibility of thechromatographic peaks, and hence their analytical value.

While a tightly packed bed is less prone to deterioration, degradationstill occurs no matter how well the packing is initially done. Vibrationduring shipping and handling, temperature fluctuations, and/or mobilephase changes can also cause the formation of voids.

Columns have been made with a plastic encasement containing the packingmaterials. However, such plastic columns tend to have poor performance.Under the pressure of a mobile phase, the plastic expands and voids areformed between the packing material and the plastic tube wall resultingin the loss of performance.

A typical plastic column is packed such that the chromatographic mediumis under initial radial compression. This radial compression is providedby the plastic wall of the column. When used, the column is furtherradially compressed under the influence of gas or liquid. To achievethis the column is placed in a pressure vessel and subjected to externalcompression pressures up to 3000 psi. This approach requires thechromatography bench to be equipped with an appropriately sizedapparatus to provide compression of the column. Such apparatus adds tothe expense of the standard chromatography work station.

A simple mechanism to impart and maintain radial compression onchromatography columns is desired.

SUMMARY OF THE INVENTION

The present invention provides a substantially permanently radiallycompressed chromatography device which does not require additionalcompression on the chromatography bench.

One embodiment of the present invention features a chromatographicdevice. The chromatographic device comprises a body having a cylindricalwall having an exterior diameter. The cylindrical wall is flexible,expanding and contracting in response to radial pressure. Thecylindrical wall defines a cavity for holding a chromatographic media. Achromatographic media is retained within the cavity. A spring elementsurrounds the cylindrical wall, permanently radially compressing thecylindrical wall and opposing the expansion of the wall in response tointernal pressure within the cavity. The radial compression prevents themovement of the chromatographic media in the column and the opening ofchannels about the walls of the column.

Preferably, the spring element is a spiral spring having spirals. Thespirals define a spring cylinder having an internal diameter less thanthe exterior diameter of the cylindrical wall in a relaxed firstposition, and defining an internal diameter greater than the exteriordiameter of the cylindrical wall in an unwound second position. Thespiral spring surrounds the cylindrical wall of body in an intermediatethird position providing radial compression on said cylindrical wall asthe spiral spring is urged to the relaxed first position.

According to the invention, a substantially permanently radiallycompressed chromatographic column is provided having a flexible-walledencasement containing chromatographic media. A spring element isdisposed surrounding the encasement and provides radial compression ofthe column.

The present invention features increased radial compression. Inaddition, the natural resiliency of the flexible walls of the encasementprevents the formation of voids during handling and shipping. Thepresent invention advantageously provides for permanent radialcompression, such that channeling and other factors which lead toperformance degradation during the use of the chromatography apparatusare substantially diminished.

The present invention also advantageously provides for a low costalternative to the prior art, dispensing with the need for expensiveradial compression apparatus on the chromatography bench.

Further advantageously, the present invention provides a chromatographiccolumn with an enhanced usable life span compared with the prior art.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features and advantages of the presentinnovation will be more fully understood from the following detaileddescription of an illustrative embodiment, taken in conjunction with theaccompanying drawing in which:

FIG. 1 depicts one aspect of a column (with cut away view) according tothe present invention;

FIG. 2 depicts the column of FIG. 1 in cross section.

FIG. 3 depicts the spring element of the column of FIG. 1;

FIG. 4 depicts a top view of the column of FIG. 1 being made accordingto the present invention; and,

FIG. 5 depicts a sleeve device embodying features of the presentinvention.

DETAILED DESCRIPTION OF AN ILLUSTRATIVE EMBODIMENT

The present invention will be described herein with reference to anillustrative embodiment of a permanently radially compressedchromatographic device in the form of a cartridge or column.

Turning now to FIG. 1, one aspect of a chromatographic column accordingto the present invention is illustrated. The chromatographic column,generally designated by the numeral 50, comprises the following majorparts: a body or column encasement 52, a spring element in the form of aspiral spring 54, and a stationary phase 56.

Encasement 52 is a plastic tube having an exterior wall 52 a andinterior wall 52 b. The interior wall 52 b defines a chamber forcontaining a packing material 56. A typical 40 mm by 10 mm cartridgewill have a total height of approximately 5.46 inches. The innerchamber, defined by inner wall 52 b has a diameter of approximately 1.57inches. The exterior wall 52 a has a diameter of approximately 1.97inches. Typical plastics for encasements are PP or HDPE.

Encasement 52 is packed with the stationary phase 56. The packing ofstationary phase 56 forces the walls of encasement 52 radially outwardas best seen in FIG. 2 and arrows aa. Typically, the stationary phase iscomprised of particles that are packed under pressure of approximately1,000 to 10,000 psi. For purposes of clarity, the stationary phase isdepicted as a solid mass.

Spiral spring 54 surrounds the cylindrical exterior wall 52 a,permanently radially compressing the cylindrical wall and opposing theexpansion of the wall in response to internal pressure within thecavity. The radial compression prevents the movement of thechromatographic media or stationary phase 56 in the column and theopening of channels about the interior walls 52 b of the column 50.

The spiral spring 54 has spirals which define a spiral cylinder 60 asbest seen in FIGS. 3 and 4. The spiral cylinder 60 has two positions. Ina first position, where spiral spring 54 is substantially relaxed, thespiral cylinder 60 has an internal diameter 60 a less than the exteriordiameter of the cylindrical wall 52 a of the encasement 52, as best seenin FIG. 4. For example, where the outside diameter of the encasement maybe approximately 1.97 inches, the spiral cylinder 60 has a diameter in afirst relaxed position of 1.75 inches. In a second position, the spiralspring 54 is unwound and under tension as depicted by arrows bb in FIG.3. In this second position, the spiral cylinder 60 has an internaldiameter 60 b greater than the exterior diameter of the cylindrical wall52 a of the encasement 52, again, as best seen in FIG. 4. The spiralspring 54, tightly surrounding the cylindrical wall 52 a of theencasement 52, in a partially unwound third position. The third positionis between the first position 60 a and the second position 60 b. In thisthird position, the spiral spring 54 provides radial compression on thecylindrical wall 52 a as the spiral cylinder 60 is urged to the relaxedfirst position 60 a.

Column 50 has a frit 70 as best seen in FIGS. 1 and 2. The frit 70serves to retain the stationary phase 56 within the encasement 52. Anend cap 72 retains the frit 70 within encasement 56. A seal 76interposed between the end cap 74 and the inner wall 52 a of theencasement 52 prevents fluid leaks. The inward radial pressure of thespring is weakest at the end of the spiral. To prevent the spiral spring54 from allowing the ends of the encasement to radially expand underpressure, spring 54 is provided with a laser weld, or other securement78. The weld or other securement 78 substantially prevents spring 54from unwinding under internal pressure created by the flow of mobilephase through the packed bed.

To facilitate the making of the column 50, a further embodiment of thepresent invention features an unwinding device, generally designated bythe numeral 80 in FIG. 5. Unwinding device 80 is comprised of a base 82,a first sleeve 84 and a second sleeve 86. First sleeve 84 and secondsleeve 86 are cylinders with an internal diameter greater than thespiral cylinder diameter in the unwound second position. Each sleeve hasmeans to receive an end of the spiral spring 54 such as clips, clamps,or openings. Preferably, spiral spring 54 has outwardly directed endswhich cooperate with slots 88 and 90 in the first and second sleeverespectively. The first and second sleeve 84 and 86 are linked to allowrotation by a cooperating interfitting rims 84 a and 86 a. Theinterfitting rims 84 a and 86 a of the first and second sleeves 84 and86 allow the first and second sleeve separate to allow removal of theencasement 52 from the unwinding device 80. First sleeve 84 is securedto base 82 to allow ease of handing and stability of the unwindingdevice 80.

A spiral spring 54 is received in the unwinding device 80 with the endsof the spring in slots 88 and 90. Rotation of the second sleeve 86 withrespect to first sleeve 84, unwind spiral spring 54. In the unwoundsecond position, spiral spring receives an encasement 52. With theencasement 52 in place, the torque placed on first sleeve 84 and secondsleeve 86 is released. The second sleeve 86 is lifted from theencasement 52, spiral spring 54 and first sleeve 84. Encasement 52 canthen be removed for first sleeve 84 as one of the ends of spiral spring54 slides through slot 88.

To make a cartridge of the present invention, encasement 52 receives afrit 70, end cap 72 and seal 76. A stationary phase is placed in theencasement and the opposite end of the encasement 52 receives a secondfrit 70, end cap 72 and seal.

Spiral spring 54 is placed in unwinding device 80, and spiral spring 54is partially unwound, by urging or twisting the ends of the spirals inthe direction of arrows bb. The partial unwinding urges the spiralcylindrical wall 60 from a relaxed first position 60 a with a smalldiameter to the second position 60 b with a larger diameter 60 b.Encasement 52 is placed inside the cylinder defined by the spirals ofthe spiral spring element 54. The unwinding torque is removed and thespiral spring 54 coils back, urged to the relaxed first position 60 a.The spiral spring 54 is prevented from fully assuming the first position60 a. The exterior wall 52 a of the encasement 52 receives the spring54. The spiral spring 54 squeezes and compresses the encasement 52 witha substantially constant radial force as represent by arrows cc as bestseen in FIG. 2.

The encasement 52 wit the spiral spring 54 is removed from the unwindingdevice by first removing the second sleeve 86. Next, the encasement 52and spiral spring 52 is removed from the first sleeve 84. The projectingends of the spiral spring 54 are preferably trimmed.

In the alternative, the stationary phase 56, frits 70, end caps 72 andseals 76 can be placed in the encasement 52 after the encasement 52 isfitted with the spiral spring 54.

Spiral spring 54 is welded at 78 to secure the end of the spring toprevent expansion and lock the diameter of the spring in place.

The present invention advantageously supplements the natural resiliencyof the flexible walls of a chromatographic cartridge with that of aspring thus maintaining the cartridge under increased radialcompression. This offers distinct advantages over metal columns, whichcannot be compressed and also over the prior art flexible wallcartridges. The inherent compression of prior art flexible wallcartridges is not sufficient to prevent the formation of voids becausethe strength of the plastic is insufficient to withstand the internalpressure, and requires additional apparatus to radially compress thecartridge when running a chromatographic analysis. The presentinvention, by permanently radially compressing the cartridge with forcessufficient to maintain uniformity of the separation medium dispenseswith numerous problems inherent in the prior art design.

Further, the present invention can be manufactured inexpensively. Theuse of the present invention is less expensive because complicatedapparatus for radially compressing the cartridge composed of a source ofpressure, a chamber, tubing, check valve(s), gauge(s), etc. is replacedby a simple device that holds the cartridge between two end connectors.

Although the illustrative embodiment has been described with referenceto a spiral spring, other springs may be used, including ribbon springsand square wire spiral springs. Further, the spring may be fashioned ofany known material exhibiting the necessary strength, for example,composites. Further, although the invention has been shown incorporatinga cartridge having a seal 76 proximate to the end of the cartridge body,the cartridge can be modified, placing the seal closer to the frit 70.In this alternative implementation, the weld 78 might be eliminated.Still further, multiple welds might be implemented in any embodiment, orthe spring might alternately be maintained by other mechanical fixingmeans.

Although the invention has been shown and described with respect toexemplary embodiments thereof, various other changes, additions andomissions in the form and detail thereof may be made therein withoutdeparting from the spirit and scope of the invention.

What is claimed is:
 1. A method for making chromatographic devicecomprising the steps of: (a.) providing a body having a cylindrical wallhaving an internal diameter and external diameter, said cylindrical wallflexible, expanding and contracting in response to radial pressure, saidcylindrical wall defines a cavity for holding a chromatographic media;(b.) placing a chromatographic media within said cavity; and, (c.)placing a spring element surrounding said cylindrical wall, permanentlyradially compressing said cylindrical wall about the external diameterand opposing the expansion of the wall in response to internal pressurewithin said cavity, said radial compression preventing the movement ofthe chromatographic media in the cavity and the opening of channelsabout the walls of the cavity.
 2. The method of claim 1, wherein saidspring element is a spiral spring having spirals which define a cylinderhaving an internal diameter less than the exterior diameter of saidcylindrical wall in a relaxed first position, and defining an internaldiameter greater than the exterior diameter of said cylindrical wall inan unwound second position, said spiral spring placed surrounding saidcylindrical wall in said second position and then released surroundingsaid cylindrical wall in a intermediate position providing radialcompression on said cylindrical wall as said spiral spring is urged tosaid relaxed first position.
 3. The method of claim 1 wherein said stepof placing a chromatographic media in said chamber is performed afterthe spring element is placed surrounding the cylindrical wall.
 4. Themethod of claim 1 wherein said step of placing a chromatographic mediain said chamber is performed before the spring element is placedsurrounding the cylindrical wall.
 5. The method of claim 1 wherein saidspring element is placed in an unwinding device said unwinding devicehaving a first sleeve and a second sleeve, each sleeve having means forreceiving an end of said spring element, each sleeve rotatably linked toallow rotation of the spring element from said relaxed first position tosaid unwound second position.